Legal Aspects of Biobanking as Key Issues for Personalized Medicine and Translational Exploitation

Timo Minssen; Jens Schovsbo

Disclosures

Personalized Medicine. 2014;11(5):497-508. 

In This Article

Legal Challenges to Biobanking

Brownsword identifies three 'bottom lines' that regulators should take into account when they design the regulatory environment for biobanks: the first one refers to the 'rights' of the biobank participants (e.g., privacy, property [including IPR] and rights arising from consent obligations); the second one is a principle that regulators should act as stewards for the agency commons to provide a supportive infrastructure for transactions and interactions between stakeholders; the third bottom line is to respect the participants' freedom to exercise their moral choice or moral responsibilities.[37]

We use Brownsword's typology because it directs attention toward the different 'layers' of the legal rules and norms that come into play and enables us to address both issues of legal dogmatic analysis (what 'rights' are relevant and under what circumstances do they arise) and of governance and policy. In the following, we will focus on the first of these bottom lines and notably on the rights associated with consent obligations and IPR. We will address the latter two bottom lines in the final remarks.

'Rights' in Biobanking

Biobanks involve both physical materials (samples) and data and legal rights can be claimed over both. As far as the physical material is concerned when the samples are collected, the legal framework is primarily established by the informed consent given by the donor. Rights to data, in other words, information that is derived from the physical material and patient interviews, as well as the resulting technologies are often debated within the framework of IPRs. The rights established by the informed consent and those that arise through IPR later on in the process of analysis are closely interrelated in the sense that the informed consent obligations establish the base line against which the legitimacy of any uses of the material must be assessed. If, for instance, the consent obligation bans commercial use, then IPR protection – at least patenting – would normally not be relevant. For this reason, the framework for any considerations involving IPR is defined by the consent obligations. This may create complications in practice in particularly regarding potentially patentable information (i.e., knowledge about the function of biological material, see more below) that arises at a late stage in a project and which was not anticipated when the project was initiated and the consents obtained. These problems are especially pertinent for novel technologies and applications, such as within the area of PM.

Basic Legal Concerns. As pointed out above, biobanks involve a great variety of stakeholders – such as donors, scientists, university and industry – with differing interests and motivations. When defining the regulatory environment it is important to be aware of these variations and in particular to take into account – and to acknowledge and accept – that motivations do not necessarily point in the same direction. Donors, for example, would often be motivated by personal interests (e.g., to help the healthcare professional with whom they have been in contact) rather than a specific and well-defined interest in the scientific project as such. This might indicate that the relationship between the donor and the project should be perceived as a long-term relationship based on trust rather than as a discreet transaction based on a 'consent' as a form of a 'contract.' To build such relationships one would need to include institutions (such as research ethics committees) and to consider also mutual commitments such as feedback obligations. The persons involved in the scientific project as researchers would often be motivated by both personal interests ('publish or perish') and general interests (furtherance of 'knowledge'). This might indicate that they would be more willing to follow the knowledge they gain from the project to wherever it takes them rather than to follow a path defined at the time of the beginning of a project. It might also lead them to act in selfish ways, for example, to protect 'their' material/results against uses by others. Even if researchers were to decide to share data, that ability may well be limited either by privacy, informed consent and confidentiality obligations or by IPR (including demands from universities). Modern universities (including also the publicly funded ones in Europe) are not only perceived as Alma Maters that bring enlightenment to society through the sharing of knowledge by teaching and publications, they are also expected to contribute to innovation in society and to capitalize on their research notably by acquiring patents and licensing these rights. This may not only close access to use university-generated knowledge but it may also create tensions between universities and their employed scientific staff, for example, regarding publication and sharing of research results. Industry is profit-driven but in order to turn knowledge derived from biobanks into commercially viable innovations that might be used to help the donors, capital from industry is essential. Unfortunately, however, this sometimes involves exclusivity obligations that may hamper data sharing.

Prior Informed Consent

Apart from fulfilling an ethical obligation and protecting autonomy informed prior consent also builds an 'environment of trust'[38] that not only encourages individual participation but is also central for the societal legitimacy of medicinal research and thus indirectly for public funding and governmental support.[39,40]

Despite its pivotal role consent obligations have for long been recognized as being problematic for a number of reasons. On a policy level, donors often do not understand (or care[41]) about the use to which they have consented.[42] For this reason the 'consent' that presupposes 'a well-reasoned decision to allow an activity' is often hollow. As seen from a normative perspective, the central legal problem is to what extent a consent is restricting uses of the material especially regarding uses that were unforeseen at the time when the sample was collected. In practice, this includes the following important questions: What uses may be initiated without going back to ask again for consent? What obligations do the consent imply on the parties? Does it, for example, include an obligation (right) to feedback[37]? If one decides to give feedback does this then include both a right for participants 'to know' and a right 'not to know', for example, about a specific disease risk?

It is difficult to provide a one size fits all answers to such questions because the term 'informed consent' covers a spectrum of different models ranging from what Cambon-Thomsen calls 'true informed consent' (i.e., a specific consent given for well-defined uses) over 'enlarged consent' and 'consent with options' to 'blanket consent'.[43] Also – and equally important – the legal framework matters greatly. If, for instance, a project involves a research ethics committee that has the competence to make decisions on behalf of the participants – such as in an opt-out system – this might influence the interpretation of consent obligations and point towards a relatively broad understanding of the wording of the obligation.

It is, therefore, not surprising that there has for the past years been an ongoing search for new models for consent. These models vary but most seek to combine traditional legal methods (e.g., an interpretation of the consent to determine what rights and obligations it provides) with an institutional setup including, for example, research ethics committees to achieve what has aptly been described as a shift from 'consent to institutions'.[44] The idea behind these initiatives is to use the consent to establish a long-term relationship between donor and project which allows the project to develop within the framework defined by the consent and the institution and which takes due account of the hopes and concerns of all the involved stakeholders. Instead of a traditional contractual approach that seeks to deal with the legal issues at the time of the establishment of the obligation (ex ante) these models are, therefore, based on an ex post (re)definition of the precise content of the obligations. A prominent example of this development is the 'dynamic consent' proposed notably by Jane Kaye, which uses modern communication strategies to inform, involve, offer choices and last but not the least obtain consent for every research project based on biobank resources.[45–48] Such developments seek to enable projects to keep going and develop but at the same time they presuppose a constant dialog between the various stakeholders or their representatives. From a legal perspective, the challenges are therefore of a diverse nature since they not only involve rulemaking in the traditional legal sense (e.g., through the formulation of consent obligations) but also the setting up and operation of the institutions.

These developments are particularly important regarding PM since the possibilities associated with these technologies are rather recent and would often not have been anticipated at the time of obtaining the consents. Also, PM presupposes access to large-scale biobanks and an effective development of PM-based treatment options requires continuous and close cross-communicative activities and exchange of information between researchers, companies, institutions, medical practitioners and patient groups. It is also often costly and industry involvement is needed which at some stage would most likely result in claims for exclusivity in one form or another. All of these issues may be problematic vis-à-vis consent obligations. Further result-oriented discussions of the various options and their advantages and disadvantages are absolutely essential to enhance the development of PM.

IPRs: Protection, Ownership & Use

First, it is important to consider which types of IPRs are relevant in the different phases of the 'lifetime' of a biobank, in particular the initial creation of the biobanks and the subsequent collection, access and use of HBM (human biological material) and associated data stored in such biobanks.[5]

During the creation phase, the biobank sets up the necessary infrastructure, for example, by potentially innovative technical equipment and software, as well as a database to store relevant material and data. If the necessary conditions are fulfilled, such infrastructures might involve patents, copyrights or – at least in the EU – database rights.[5] The manner in which the biobank is established might also be considered as a valuable trade secret, since it could determine the quality of the HBM, associated data and the services provided by the biobank. During the collection phase, the biobank starts to collect material and data from different sources and arrange them – according to certain (selection) criteria – in a database. The method of arranging the material and data in the database might have an important impact on the quality and/or value of the database and the extent to which users can search the database. Once again, such arrangements or compilation of material and data might be the object of sui generis database protection.[49] Furthermore, trademark rights might be obtained in relation to the name of the biobank, its database or the services it provides. During the access phase, it is for instance uncertain to which extent HBM stored in the biobank could be the object of upstream patent rights, since HBM could be considered as natural products isolated from the human body. While such patent rights have indeed been granted, the patentability of, for example (isolated) DNA, stem cells and – most importantly – methods and particular applications useful in diagnostics and PM remains much debated.[50,51] Finally, the question arises as to which extent the rights of the donors/patients limit the possibilities to obtain IPRs in relation to HBM and data stored in the biobank. During the use phase, the approved applicant uses the HBM and data for research purposes. Such use might also result in patentable inventions further downstream or various forms of regulatory exclusivities and trade secrets.

This brings us to the second layer of questions that need to be addressed. One of these includes the issue of ownership. This is a complicated question that often involves both IPRs and contractual rules and interests. As a starting point, the IPR legislation identifies the beneficiaries of the protection. The rights under the database rules are, for example, granted to the entity that has made the investment in the establishment of the protected database. For databases that are run by research institutions, this means that normally both the institution, individual researchers, and funders may claim – and obtain – rights in the database simultaneously. For inventions that arise through employment, the right to apply for patent protection would often belong to the employer, but the inventor himself/herself (being the researcher/group of researchers who has made the patentable invention) may also have certain rights. The rights arising under IPR can normally be transferred by contract, and often research collaboration would involve such transfer. It is therefore also a specific issue under which conditions a biobank could or should become co-owner of patent rights on inventions resulting from the use of the material and data that it provided, selected and possibly processed for the specific research (so-called downstream IPRs). This entails investigating how to reach a balance between the exclusive nature of IPRs and the requirement of funding agencies to share the data that result from research on the basis of HBM and associated data.[52] Another issue concerns the modalities and conditions for use of the information derived from the biobank including the choice between an 'open' model and a 'closed' one or a combination thereof. Even though there are in-built tensions between the rules of IPR (and privacy) and the norms underpinning these systems and the principles of 'openness' and 'data sharing', it is important to bear in mind that IPRs do not necessarily have to be translated into 'closed' models. Instead, right holders may well use the control over information provided to them by the IPR rules on exclusivity to find the right balance in what has been described as "the spectrum between free use of knowledge by anyone for any purpose, to exclusive use by one entity for its own use".[53] One example of this could be found in the context of open licensing where a failure by a licensee to comply with a reciprocity obligation to (continue to) secure open access to subsequent user could be enforced through copyright (and/or contract). Other examples of the nontraditional options which IPR may provide include the use by patient groups that have established tissue and data banks and have negotiated directly with researchers under agreements by contracts that entitle them to manage IPR rights arising from the research so as to secure access to diagnostics and therapeutics at reasonable prices.[38,54] Therefore, the mere acquisition of IPR does not imply any specific modalities for rights administration. Instead, it necessitates a need for decisions and agreements to be made, and to be aware of the consequences that various choices would entail.

This appears to be particularly important within the area of PM. The potential healthcare benefits offered by advances in PM are substantial and, therefore, the public need is often acute. However, and as pointed out above, developing commercial treatment/diagnostic methods regarding PM can be very costly and therefore industry involvement is often essential. In order to obtain the necessary information to personalized treatment and such, access to large-scale biobanks is crucial. This may also necessitate (international) cooperation between different institutions. The industry has also realized that cutting-edge advance within PM and the development of truly innovative biologics and methods is extremely expensive and difficult to achieve within the traditional 'closed innovation' model. New strategic partnerships with competitors, smaller specialized biotech companies or in the form of PPPs are often necessary to develop breakthrough drugs. However, due to the immense risks and costs associated with pharmaceutical R&D and clinical trials, the industry and investors would – at least at some stage – normally require some type of exclusivity, that is, be it through patent-related rights and licenses, regulatory exclusivities or trade secrets.[55,56] Therefore, determining the right balance between openness and exclusivity is particularly decisive but also complex here.

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